Twenty-five years ago,Nembrot and colleagues reported amplification of the estrogen receptor alpha gene(ESR1) in breast cancer,initiating a broad and still ongoing scientific debate on the prevalence and clinical sign...Twenty-five years ago,Nembrot and colleagues reported amplification of the estrogen receptor alpha gene(ESR1) in breast cancer,initiating a broad and still ongoing scientific debate on the prevalence and clinical significance of this genetic aberration,which affects one of the most important genes in breast cancer.Since then,a multitude of studies on this topic has been published,covering a wide range of divergent results and arguments.The reported prevalence of this alteration in breast cancer ranges from 0% to 75%,suggesting that ESR1 copy number analysis is hampered by technical and interpreter issues.To date,two major issues related to ESR1 amplification remain to be conclusively addressed:(1) The extent to which abundant amounts of messenger RNA can mimic amplification in standard fluorescence in situ hybridization assays in the analysis of strongly expressed genes like ESR1,and(2) the clinical relevance of ESR1 amplification:Such relevance is strongly disputed,with data showing predictive value for response as well as for resistance of the cancer to anti-estrogen therapies,or for subsequent development of cancers in the case of precursor lesions that display amplification of ESR1.This review provides a comprehensive summary of the various views on ESR1 amplification,and highlights explanations for the contradictions and conflicting data that could inform future ESR1 research.展开更多
This study sought to elucidate the role of the Pvull and Xbal polymorphisms of the estrogen receptor gene in 74 Chinese patients with multiple sclerosis, and 95 ethnicity-matched controls, using polymerase chain react...This study sought to elucidate the role of the Pvull and Xbal polymorphisms of the estrogen receptor gene in 74 Chinese patients with multiple sclerosis, and 95 ethnicity-matched controls, using polymerase chain reaction-restriction fragment-length polymorphism analysis. The results revealed that the P allele of Pvull was significantly more prevalent in multiple sclerosis patients compared with controls （P = 0.019）. While distribution frequencies were significantly increased in female multiple sclerosis patients compared with female controls （P = 0.044）, no significant difference was observed between male patients and controls （P〉 0.05）. Frequencies of Ppxx genotypes were significantly higher in multiple sclerosis patients compared with controls （24.3% vs 12.8%, P = 0.025）. Genotypes and alleles of the estrogen receptor were not associated with age, number of attacks or expanded disability status scale scores of patients with multiple sclerosis. These findings indicate that the Pvull but not the Xbal polymorphism in the estrogen receptor gene is associated with susceptibility to multiple sclerosis in the Chinese population. In addition, women with P allele appear to be particularly susceptible to multiple sclerosis.展开更多
Estrogen plays important regulatory and protective roles in the central nervous system through estrogen receptor a mediation. Previous studies applied eukaryotic expression and lentiviral vectors carrying estrogen rec...Estrogen plays important regulatory and protective roles in the central nervous system through estrogen receptor a mediation. Previous studies applied eukaryotic expression and lentiviral vectors carrying estrogen receptor a to cladfy the underlying mechanisms. In the present study, an adenovirus vector expressing the mouse full estrogen receptor a gene was constructed to identify biological characteristics of estrogen receptor a recombinant adenovirus infecting nerve cells. Primary cultured mouse nerve cells were first infected with estrogen receptor a recombinant adenovirus at various multiplicities of infection, followed by 100 multiplicity of infection. Results showed overexpression of estrogen receptor α mRNA and protein in the infected nerve cells. Estrogen receptor a recombinant adenovirus at 100 multiplicity of infection successfully infected neurons and upregulated estrogen receptor a mRNA and protein expression.展开更多
Objective: To investigate the relationship between estrogen receptor(ER) gene and the clinical indexes associated with coronary heart disease (CHD). Methods: By means of polymerase chain reaction-restriction fragment ...Objective: To investigate the relationship between estrogen receptor(ER) gene and the clinical indexes associated with coronary heart disease (CHD). Methods: By means of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), we analyzed ER gene polymorphism in 84 CHD patients and 61 healthy subjects and non-CHD inpatients. The clinical indexes associated with CHD were analyzed in relation to the three ER genotypes. Results: There were significant differences in the incidence of hypertension (58.62%), fibrinogen (Fib) concentration (3.5±0.8 g/L), body mass index (BMI, 25.1±3.2), HDL-C concentration (1.0±0.2 mmol/L) between PP genotype group and other genotype groups (P<0.05). Conclusion: ER gene polymorphism may affect ER-mediated cardiovascular protective effect by modulating the expression of ER.展开更多
The correlation or serum estradiol concentrstion and uterine estrogen receptor (ER) gene expression (ERn and ERc quantitated by Dextrsn Coat Charcoal assay and ER mRNA by Northern blotting) was studied during the rat ...The correlation or serum estradiol concentrstion and uterine estrogen receptor (ER) gene expression (ERn and ERc quantitated by Dextrsn Coat Charcoal assay and ER mRNA by Northern blotting) was studied during the rat estrous cycle and early Pregnant stage (dl-d10). The ER gone expression was up - regulated by estrogen and the levels of ER mRNA synchronized with the changes of ER protein, suggesting that estrogen influenced the trsnscriPtional step of the ER gene. Post-coitum ER expression increased with the serum estrsdiol progressively, reached a peak on d4-ds (Just before implantation), but drastically dropped to the nadir on d6-d7 (during implantation) and then recovered. It was of interest to discover that ER mRNA level in the nonimplantstion sites (NIS) of uterus was much higher than that in the implantstion sites (IS).展开更多
Objective:To explore the mechanism of the estrogen-like effect of genistein by observing the expression of Matrix metalloproteinases-26(MMP-26)and ERa in human endometrial cancer cells(Ishikawa and HEC-1B)in vitro.Met...Objective:To explore the mechanism of the estrogen-like effect of genistein by observing the expression of Matrix metalloproteinases-26(MMP-26)and ERa in human endometrial cancer cells(Ishikawa and HEC-1B)in vitro.Methods:The effect of genistein on MMP-26 and ERa expression was examined by western blot in cultured Ishikawa and HEC-1B cells.Additionally,the effects of genistein on ERa-ERE-luc and ERb-ERE-luc reporter gene expression in HEC-1B cells were analyzed by luciferase activity assays.Results:MMP-26 and ERa protein expression was down-regulated by genistein treatment in Ishikawa cell induced by high concentration E2,whereas MMP-26 and ERa protein expression was up-regulated by genistein treatment in Ishikawa cells induced by low concentration E2.Expression of the ERa-ERE-luc and ERb-ERE-luc reporter genes was significantly increased after E2 induction and was further up-regulated by genistein.Expression of ERa-ERE-luc and ERb-ERE-luc reporter genes decreased significantly following genistein treatment in high E2 concentrations,and increased significantly following genistein treatment in low E2 concentrations.Conclusions:Genistein showed estrogen-like effects in endometrial cancer cells and influenced estrogen receptor signaling by modulating ERa and ERb expression.展开更多
Dopamine agonists （DA） are a first-line therapy for prolactinomas （PA）. However, nearly 10% of prolactinomas do not respond to DA therapy. A considerable number of studies have shown that estrogen plays an importa...Dopamine agonists （DA） are a first-line therapy for prolactinomas （PA）. However, nearly 10% of prolactinomas do not respond to DA therapy. A considerable number of studies have shown that estrogen plays an important role in the development of prolactinomas. However, the expression of estrogen receptors （ER） in prolactinomas has not been fully explored. Accordingly, we examined the levels of ESR1 and its subtypes A5-DeI-ESR1 and ESR2 mRNA in prolactinomas. In the present study,展开更多
Breast cancer is the leading cause of death in women. Prognosis of breast cancer is often pessimistic because the tumors are prone to metastasizing to the bone, brain, and lung. The estrogen signaling receptor (ESR) p...Breast cancer is the leading cause of death in women. Prognosis of breast cancer is often pessimistic because the tumors are prone to metastasizing to the bone, brain, and lung. The estrogen signaling receptor (ESR) pathway contains 39 main genes and proteins which makes it one of the larger signaling pathways. Predominately this pathway and the proteins within are involved in breast growth and development, making it a prospective area of study for breast cancer. While the healthy ESR pathway has been constructed and is well established, a mechanistic model of mutated genes of ESR pathway has not been delved upon. Such mutated models could be utilized for selecting combinational targets for drug therapies, as well as elucidating crosstalk between other pathways and feedback mechanisms. To construct the mutated models of the ESR pathway it is imperative to assess what is currently understood in the literature and what inconsistencies exist in order to resolve them. Without this information, a model of the ESR pathway will be unreliable and likely unproductive. This review is the detailed literature survey of the biological studies performed on ESR pathways genes, and their respective roles in breast cancer. Furthermore, the details mentioned in the review can be beneficial for the integrated study of the ESR pathway genes, which includes, structural and dynamics study of the genes products, to have a holistic understanding of the cancer mechanism.展开更多
Estrogen receptors and E2F transcription factors are the key players of two nuclear signaling pathways which exert a major role in oncogenesis, particularly in the mammary gland. Different levels of dialogue between t...Estrogen receptors and E2F transcription factors are the key players of two nuclear signaling pathways which exert a major role in oncogenesis, particularly in the mammary gland. Different levels of dialogue between these two pathways have been deciphered and deregulation of the E2F pathway has been shown to impact the response of breast cancer cells to endocrine therapies. The present review focuses on the transcriptional coregulator RIP140/NRIP1 which is involved in several regulatory feed-back loops and inhibitory cross-talks between different nuclear signaling pathways. RIP140 regulates the transactivation potential of estrogen receptors and E2Fs and is also a direct transcriptional target of these transcription factors. Published data highlight the complex regulation of RIP140 expression at the transcriptional level and its potential role in transcription cross-talks. Indeed, a subtle regulation of RIP140 expression levels has important consequences on other transcription networks targeted by this coregulator. Another level of regulation implies titration mechanisms by which activation of a pathway leads to sequestration of the RIP140 protein and thus impinges other gene regulatory circuitries. Altogether, RIP140 occupies a place of choice in the dialogue between nuclear receptors and E2Fs, which could be highly relevant in various human pathologies such as cancer or metabolic diseases.展开更多
文摘Twenty-five years ago,Nembrot and colleagues reported amplification of the estrogen receptor alpha gene(ESR1) in breast cancer,initiating a broad and still ongoing scientific debate on the prevalence and clinical significance of this genetic aberration,which affects one of the most important genes in breast cancer.Since then,a multitude of studies on this topic has been published,covering a wide range of divergent results and arguments.The reported prevalence of this alteration in breast cancer ranges from 0% to 75%,suggesting that ESR1 copy number analysis is hampered by technical and interpreter issues.To date,two major issues related to ESR1 amplification remain to be conclusively addressed:(1) The extent to which abundant amounts of messenger RNA can mimic amplification in standard fluorescence in situ hybridization assays in the analysis of strongly expressed genes like ESR1,and(2) the clinical relevance of ESR1 amplification:Such relevance is strongly disputed,with data showing predictive value for response as well as for resistance of the cancer to anti-estrogen therapies,or for subsequent development of cancers in the case of precursor lesions that display amplification of ESR1.This review provides a comprehensive summary of the various views on ESR1 amplification,and highlights explanations for the contradictions and conflicting data that could inform future ESR1 research.
基金the National Natural Science Foundation of China, No. 81071148
文摘This study sought to elucidate the role of the Pvull and Xbal polymorphisms of the estrogen receptor gene in 74 Chinese patients with multiple sclerosis, and 95 ethnicity-matched controls, using polymerase chain reaction-restriction fragment-length polymorphism analysis. The results revealed that the P allele of Pvull was significantly more prevalent in multiple sclerosis patients compared with controls （P = 0.019）. While distribution frequencies were significantly increased in female multiple sclerosis patients compared with female controls （P = 0.044）, no significant difference was observed between male patients and controls （P〉 0.05）. Frequencies of Ppxx genotypes were significantly higher in multiple sclerosis patients compared with controls （24.3% vs 12.8%, P = 0.025）. Genotypes and alleles of the estrogen receptor were not associated with age, number of attacks or expanded disability status scale scores of patients with multiple sclerosis. These findings indicate that the Pvull but not the Xbal polymorphism in the estrogen receptor gene is associated with susceptibility to multiple sclerosis in the Chinese population. In addition, women with P allele appear to be particularly susceptible to multiple sclerosis.
基金Research Project of Science and Technology Department of Guizhou Province,No.sy[2009]3054
文摘Estrogen plays important regulatory and protective roles in the central nervous system through estrogen receptor a mediation. Previous studies applied eukaryotic expression and lentiviral vectors carrying estrogen receptor a to cladfy the underlying mechanisms. In the present study, an adenovirus vector expressing the mouse full estrogen receptor a gene was constructed to identify biological characteristics of estrogen receptor a recombinant adenovirus infecting nerve cells. Primary cultured mouse nerve cells were first infected with estrogen receptor a recombinant adenovirus at various multiplicities of infection, followed by 100 multiplicity of infection. Results showed overexpression of estrogen receptor α mRNA and protein in the infected nerve cells. Estrogen receptor a recombinant adenovirus at 100 multiplicity of infection successfully infected neurons and upregulated estrogen receptor a mRNA and protein expression.
基金Supported by the Key Basic Research and Development Project of National "973" Program of China (G200057008) the Foundation for University Leading Teachers Sponsored by the Ministry of Education of China, and by Funds for Key Natural Science Research of
文摘Objective: To investigate the relationship between estrogen receptor(ER) gene and the clinical indexes associated with coronary heart disease (CHD). Methods: By means of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), we analyzed ER gene polymorphism in 84 CHD patients and 61 healthy subjects and non-CHD inpatients. The clinical indexes associated with CHD were analyzed in relation to the three ER genotypes. Results: There were significant differences in the incidence of hypertension (58.62%), fibrinogen (Fib) concentration (3.5±0.8 g/L), body mass index (BMI, 25.1±3.2), HDL-C concentration (1.0±0.2 mmol/L) between PP genotype group and other genotype groups (P<0.05). Conclusion: ER gene polymorphism may affect ER-mediated cardiovascular protective effect by modulating the expression of ER.
文摘The correlation or serum estradiol concentrstion and uterine estrogen receptor (ER) gene expression (ERn and ERc quantitated by Dextrsn Coat Charcoal assay and ER mRNA by Northern blotting) was studied during the rat estrous cycle and early Pregnant stage (dl-d10). The ER gone expression was up - regulated by estrogen and the levels of ER mRNA synchronized with the changes of ER protein, suggesting that estrogen influenced the trsnscriPtional step of the ER gene. Post-coitum ER expression increased with the serum estrsdiol progressively, reached a peak on d4-ds (Just before implantation), but drastically dropped to the nadir on d6-d7 (during implantation) and then recovered. It was of interest to discover that ER mRNA level in the nonimplantstion sites (NIS) of uterus was much higher than that in the implantstion sites (IS).
基金by National Nature Funds(No.30510403202)National Ministry of Education(No.IRT0413)Doctor Funds supported by National Ministry of Education(No.20050026012 and 20060026019).
文摘Objective:To explore the mechanism of the estrogen-like effect of genistein by observing the expression of Matrix metalloproteinases-26(MMP-26)and ERa in human endometrial cancer cells(Ishikawa and HEC-1B)in vitro.Methods:The effect of genistein on MMP-26 and ERa expression was examined by western blot in cultured Ishikawa and HEC-1B cells.Additionally,the effects of genistein on ERa-ERE-luc and ERb-ERE-luc reporter gene expression in HEC-1B cells were analyzed by luciferase activity assays.Results:MMP-26 and ERa protein expression was down-regulated by genistein treatment in Ishikawa cell induced by high concentration E2,whereas MMP-26 and ERa protein expression was up-regulated by genistein treatment in Ishikawa cells induced by low concentration E2.Expression of the ERa-ERE-luc and ERb-ERE-luc reporter genes was significantly increased after E2 induction and was further up-regulated by genistein.Expression of ERa-ERE-luc and ERb-ERE-luc reporter genes decreased significantly following genistein treatment in high E2 concentrations,and increased significantly following genistein treatment in low E2 concentrations.Conclusions:Genistein showed estrogen-like effects in endometrial cancer cells and influenced estrogen receptor signaling by modulating ERa and ERb expression.
基金supported by the Research Special Fund for Public Welfare Industry of Health(201402008)
文摘Dopamine agonists （DA） are a first-line therapy for prolactinomas （PA）. However, nearly 10% of prolactinomas do not respond to DA therapy. A considerable number of studies have shown that estrogen plays an important role in the development of prolactinomas. However, the expression of estrogen receptors （ER） in prolactinomas has not been fully explored. Accordingly, we examined the levels of ESR1 and its subtypes A5-DeI-ESR1 and ESR2 mRNA in prolactinomas. In the present study,
文摘Breast cancer is the leading cause of death in women. Prognosis of breast cancer is often pessimistic because the tumors are prone to metastasizing to the bone, brain, and lung. The estrogen signaling receptor (ESR) pathway contains 39 main genes and proteins which makes it one of the larger signaling pathways. Predominately this pathway and the proteins within are involved in breast growth and development, making it a prospective area of study for breast cancer. While the healthy ESR pathway has been constructed and is well established, a mechanistic model of mutated genes of ESR pathway has not been delved upon. Such mutated models could be utilized for selecting combinational targets for drug therapies, as well as elucidating crosstalk between other pathways and feedback mechanisms. To construct the mutated models of the ESR pathway it is imperative to assess what is currently understood in the literature and what inconsistencies exist in order to resolve them. Without this information, a model of the ESR pathway will be unreliable and likely unproductive. This review is the detailed literature survey of the biological studies performed on ESR pathways genes, and their respective roles in breast cancer. Furthermore, the details mentioned in the review can be beneficial for the integrated study of the ESR pathway genes, which includes, structural and dynamics study of the genes products, to have a holistic understanding of the cancer mechanism.
文摘Estrogen receptors and E2F transcription factors are the key players of two nuclear signaling pathways which exert a major role in oncogenesis, particularly in the mammary gland. Different levels of dialogue between these two pathways have been deciphered and deregulation of the E2F pathway has been shown to impact the response of breast cancer cells to endocrine therapies. The present review focuses on the transcriptional coregulator RIP140/NRIP1 which is involved in several regulatory feed-back loops and inhibitory cross-talks between different nuclear signaling pathways. RIP140 regulates the transactivation potential of estrogen receptors and E2Fs and is also a direct transcriptional target of these transcription factors. Published data highlight the complex regulation of RIP140 expression at the transcriptional level and its potential role in transcription cross-talks. Indeed, a subtle regulation of RIP140 expression levels has important consequences on other transcription networks targeted by this coregulator. Another level of regulation implies titration mechanisms by which activation of a pathway leads to sequestration of the RIP140 protein and thus impinges other gene regulatory circuitries. Altogether, RIP140 occupies a place of choice in the dialogue between nuclear receptors and E2Fs, which could be highly relevant in various human pathologies such as cancer or metabolic diseases.
